BME 418, Quantitative Cell BiologyAlan J. HuntLecture #27: Electrically excitable cells and vesicle fusionAs we've already discussed, cells need to transport substances in and out across the cytoplasmic membrane (e.g. ECM, nutrients, and hormones). Some substances readily diffuse across lipid bilayer and do not require any specialized transport mechanisms. Other substances cross the membrane via specific channels or integral membrane transporters. However, there are two cases where these are inadequate:-Large molecules (e.g. collagen, ECM, peptides)-Substance that must be released abruptly (NT's, some hormones).Freeze-etch SEM of synaptic vesicles.In these cases substance are sequestered into membraneous sacs called vesicles, which reside in the cytosol. In response to an appropriate stimulus vesicles fuse with the plasma membrane and their contents are extruded from the cell. Examples:-ECM, blood proteins (e.g. albumin).-Insulin release from pancreatic cells following sugar consumption.-Histamine release from mast cells (allergies).-Neurotransmitter (NT) release-Exocytosis of cholesterol-containing lipoprotein particles (e.g. HDL, VLDL).All of these processes are common sites of therapeutic manipulation. This is largely because processes that occur outside of a cell are more accessible; most extracellular

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BME 418, Quantitative Cell BiologyAlan J. Hunttargets will be exposed to any chemicals in the blood stream. One important counter example is neural tissue, which is shielded by the “brain-blood barrier”. A schematic of the Blood Brain Barrier with associated astrocytes (from: ) All of these exocytotic processes share similar mechanisms. For brevity we will focus on one, NT release. Before pursuing this, a discussion of how neurons work is in order. HydraFlatwormEarthworm(from )With the advent of multicellular life came the need for communication between the cells that make up an organism. For many purposes this can be accomplished by direct mechanical interactions or through excreted chemical messengers. But for activities such as locomotion and higher level processing there is a requirement for signaling that is fast, spatially targeted, and can encode a great deal of information. In most multicellular organisms this is accomplished by nervous systems.

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